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asthma pathophysiology

Aran Singanayagam, Andrew I Ritchie, Sebastian L Johnston
PURPOSE OF REVIEW: The emergence of next-generation 16S rRNA sequencing techniques has facilitated a more detailed study of the body's microbiota and led to renewed interest in the association between microbial exposure and asthma inception. In this review, we evaluate the evidence that the respiratory tract and intestinal microbiota contribute to asthma pathogenesis and progression. RECENT FINDINGS: Human studies have revealed associations between the presence of potentially pathogenic bacteria in the respiratory tract in early life and subsequent risk of allergic sensitization and asthma...
October 15, 2016: Current Opinion in Pulmonary Medicine
Edith Chen, Madeleine U Shalowitz, Rachel E Story, Katherine B Ehrlich, Cynthia S Levine, Robin Hayen, Adam K K Leigh, Gregory E Miller
OBJECTIVES: The objective of this study was to investigate 2 key dimensions of socioeconomic status (SES)-prestige and resources-and their associations with immune, behavioral, and clinical outcomes in childhood asthma. METHODS: Children ages 9 to 17 years with a physician's diagnosis of asthma (N = 150), and one of their parents participated in this study. Children and parents completed interviews and questionnaires about SES (prestige = parent education; resources = family assets), environmental exposures, and clinical asthma measures...
September 30, 2016: Psychosomatic Medicine
Yuan Ma, Jia-Xiang Zhang, Ya-Nan Liu, Ai Ge, Hao Gu, Wang-Jian Zha, Xiao-Ning Zeng, Mao Huang
In the pathophysiology of asthma, structural cell dysfunction and concomitant microenvironment changes in airways are crucial to pathological progression, which involves oxidative stress. Caffeic acid phenethyl ester (CAPE) is an active anti-oxidative component obtained from propolis, and has been shown to have beneficial effects on several respiratory disorders, such as chronic obstructive pulmonary disease and lung cancer. However, the impact of CAPE on asthma is not well understood. Therefore, this study investigated the advantages of using CAPE to treat asthma and demonstrated the roles of CAPE in the regulation of airway microenvironments...
October 13, 2016: Free Radical Biology & Medicine
Cecilia K Andersson, Alexandra Adams, Prasad Nagakumar, Cara Bossley, Atul Gupta, Daphne De Vries, Afiqah Adnan, Andrew Bush, Sejal Saglani, Clare M Lloyd
BACKGROUND: Neutrophils and IL-17A have been linked mechanistically in models of allergic airways disease and have been associated with asthma severity. However, their role in paediatric asthma is unknown. OBJECTIVES: To investigate the role of neutrophils and the IL-17A pathway in mediating paediatric severe therapy resistant asthma (STRA). METHODS: Children with STRA (n=51, age 12.6 (6 -16.3) years) and non-asthmatic controls (n=15, age 4...
October 13, 2016: Journal of Allergy and Clinical Immunology
Mauro Maniscalco, Debora Paris, Dominique J Melck, Maria D'Amato, Anna Zedda, Matteo Sofia, Cristiana Stellato, Andrea Motta
BACKGROUND: Epidemiological and clinical evidence supports the existence of an obesity-related asthma phenotype. No distinct pathophysiological elements or specific biomarkers have been identified so far but increased oxidative stress has been reported. OBJECTIVE: We aimed at verifying whether metabolomics of exhaled breath condensate (EBC) from obese asthmatic (OA), lean asthmatic (LA) and obese non-asthmatic (ONA) patients could recognize specific, statistically validated biomarkers for a separate "asthma-obesity" respiratory metabolic phenotype, here defined as "metabotype"...
October 13, 2016: Journal of Allergy and Clinical Immunology
Y S Prakash
Airway structure and function are key aspects of normal lung development, growth and aging, as well as of lung responses to the environment and the pathophysiology of important diseases such as asthma, COPD and fibrosis. In this regard, the contributions of airway smooth muscle (ASM) are both functional, in the context of airway contractility and relaxation, as well as synthetic, involving production and modulation of extracellular components, modulation of the local immune environment, cellular contribution to airway structure, and finally, interactions with other airway cell types such as epithelium, fibroblasts and nerves...
October 14, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Yen Leong Chua, Ka Hang Liong, Chiung-Hui Huang, Hok Sum Wong, Qian Zhou, Say Siong Ler, Yafang Tang, Chin Pei Low, Hui Yu Koh, I-Chun Kuo, Yongliang Zhang, W S Fred Wong, Hong Yong Peh, Hwee Ying Lim, Moyar Qing Ge, Angela Haczku, Veronique Angeli, Paul A MacAry, Kaw Yan Chua, David M Kemeny
Previous studies have highlighted the importance of lung-draining lymph nodes in the respiratory allergic immune response, whereas the lung parenchymal immune system has been largely neglected. We describe a new in vivo model of respiratory sensitization to Blomia tropicalis, the principal asthma allergen in the tropics, in which the immune response is focused on the lung parenchyma by transfer of Th2 cells from a novel TCR transgenic mouse, specific for the major B. tropicalis allergen Blo t 5, that targets the lung rather than the draining lymph nodes...
October 12, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Paula J Busse, Janette M Birmingham, Agustin Calatroni, Joseph Manzi, Anna Goryachokovsky, Giselle Fontela, Alex Federman, Juan Wisnivesky
BACKGROUND: Aged asthma patients experience increased morbidity and mortality. Knowledge of the aging effect on airway inflammation and asthma control is limited. OBJECTIVE: To compare airway inflammation and its relationship with asthma control in aged vs. younger patients and determine if differences are asthma-specific or due to "inflamm-aging." METHODS: Prospective study of aged (>60 years) and younger (21-40 years) inner-city asthma patients...
October 7, 2016: Journal of Allergy and Clinical Immunology
Masamichi Yamashita
Aspirin is the oldest non-steroidal anti-inflammatory drug (NSAID), and it sometimes causes asthma-like symptoms known as aspirin-exacerbated respiratory disease (AERD), which can be serious. Unwanted effects of aspirin (aspirin intolerance) are also observed in patients with food-dependent exercise-induced anaphylaxis, a type I allergy disease, and aspirin-induced urticaria (AIU). However the target and the mechanism of the aspirin intolerance are still unknown. There is no animal or cellular model of AERD, because its pathophysiological mechanism is still unknown, but it is thought that inhibition of cyclooxygenase by causative agents lead to an increase of free arachidonic acid, which is metabolized into cysteinyl leukotrienes (cysLTs) that provoke airway smooth muscle constriction and asthma symptoms...
October 5, 2016: Current Drug Targets
Detlef Neumann
Histamine is a pro-inflammatory mediator with a prominent role in allergic diseases. Antagonists at the histamine receptor subtype 1 are central in anti-allergic therapies, with the exception of allergic asthma, where they are clinically without effect. The latest identified histamine receptor subtype 4, which is expressed mainly in hematopoietic cells, now provides a reasonable target for new therapeutic strategies inhibiting histamine function. The pathophysiology of allergy, esp. allergic asthma, and in its context the effects of antagonists at the histamine receptor subtype 4 in preclinical and clinical settings are discussed in this chapter...
October 8, 2016: Handbook of Experimental Pharmacology
Andrew R Parker, Andrew G Ayars, Matthew C Altman, William R Henderson
Aspirin-exacerbated respiratory disease (AERD) is a syndrome of severe asthma and rhinosinusitis with nasal polyposis with exacerbations of baseline eosinophil-driven and mast cell-driven inflammation after nonsteroidal antiinflammatory drug ingestion. Although the underlying pathophysiology is poorly understood, dysregulation of the cyclooxygenase and 5-lipoxygenase pathways of arachidonic acid metabolism is thought to be key. Central features of AERD pathogenesis are overproduction of proinflammatory and bronchoconstrictor cysteinyl leukotrienes and prostaglandin (PG) D2 and inhibition of bronchoprotective and antiinflammatory PGE2...
November 2016: Immunology and Allergy Clinics of North America
Sandeep Puranik, Erick Forno, Andrew Bush, Juan C Celedón
Severe exacerbations negatively impact the quality of life and education of children with asthma, while also causing substantial healthcare costs. Preventing severe asthma exacerbations requires identifying patients at high risk, in order to develop personalized care protocols to prevent such exacerbations. In this review, we assess and discuss recently published data on risk factors and predictive tools for severe asthma exacerbations in childhood. Although few genome-wide association studies have focused on severe asthma exacerbations, one such study recently identified cadherin-related family member 3 (CDHR3, implicated on integrity of the airway epithelium), as a susceptibility gene for recurrent severe asthma exacerbations in young children...
October 6, 2016: American Journal of Respiratory and Critical Care Medicine
Fernando Maria de Benedictis, Andrew Bush
Wheeze is a common symptom in young children and is usually associated with viral illnesses. It is a major source of morbidity and is responsible for a high consumption of healthcare and economic resources worldwide. A few children have a condition resembling classical asthma. Rarer specific conditions may have a wheezy component and should be considered in the differential diagnosis. Over the last half century, there have been many circular discussions about the best way of managing preschool wheeze. In general, intermittent wheezing should be treated with intermittent bronchodilator therapy, and a controller therapy should be prescribed for a young child with recurrent wheezing only if positively indicated, and only then if carefully monitored for efficacy...
October 4, 2016: Archives of Disease in Childhood
Alexander J Adami, Sonali J Bracken
Asthma is a highly heterogeneous disease characterized by inflammation of the airways, which invokes symptoms such as wheeze, dyspnea, and chest tightness. Asthma is the product of multiple interconnected immunological processes and represents a constellation of related, but distinct, disease phenotypes. The prevalence of asthma has more than doubled since the 1980s, and efforts to understand this increase have inspired consideration of the microbiome as a key player in the pathophysiology and regulation of this disease...
September 2016: Yale Journal of Biology and Medicine
Jatinder Singh, Ramanpreet Shah, Dhandeep Singh
Asthma is inveterate inflammatory disorder, delineated by airway inflammation, bronchial hyperresponsiveness (BHR) and airway wall remodeling. Although, asthma is a vague term, and is recognized as heterogenous entity encompassing different phenotypes. Targeting single mediator or receptor did not prove much clinical significant, as asthma is complex disease involving myriad inflammatory mediators. Asthma may probably involve a large number of different types of molecular and cellular components interacting through complex pathophysiological pathways...
September 22, 2016: Pulmonary Pharmacology & Therapeutics
T Pincez, L Calamy, Z Germont, A Lemoine, A-A Lopes, A Massiot, J Tencer, C Thivent, A Hadchouel
Acute and chronic pulmonary complications are frequent in sickle cell disease (SCD), with different spectrum and characteristics in children and adults. Chronic hypoxia is frequent and plays a role in several respiratory complications in SCD. Furthermore, hypoxia has been associated with a higher risk of cerebral ischemia. Despite differing oxygen affinity between hemoglobin A and S, standard pulse oximetry was shown to be accurate in diagnosing hypoxia in SCD patients. Whereas acute hypoxia management is similar to non-SCD patients, chronic hypoxia treatment is mainly based on a transfusion program rather than long-term oxygen therapy...
October 2016: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
Stephan Löser, Lisa G Gregory, Youming Zhang, Katrein Schaefer, Simone A Walker, James Buckley, Laura Denney, Charlotte H Dean, William O C Cookson, Miriam F Moffatt, Clare M Lloyd
BACKGROUND: Genome-wide association studies have identified the ORMDL3 (ORM (yeast)-like protein isoform 3) gene locus on human chromosome 17q to be a highly significant risk factor for childhood-onset asthma. OBJECTIVE: We sought to investigate in vivo the functional role of ORMDL3 in disease inception. METHODS: An Ormdl3 deficient mouse was generated and the role of ORMDL3 in the generation of allergic airways disease to the fungal aeroallergen Alternaria alternata determined...
September 10, 2016: Journal of Allergy and Clinical Immunology
Diego Jose Maselli, Maria Ines Velez, Linda Rogers
Interleukin-5, an important cytokine in the pathophysiology of asthma, participates in terminal maturation and increases chemotaxis, endothelial adhesion, and activation of eosinophils. Blockade of interleukin-5 activity with monoclonal antibodies have been successful in decreasing eosinophil counts. Reslizumab, a monoclonal antibody that targets interleukin-5, has been studied for the treatment of severe asthma. Several studies have shown that reslizumab can effectively treat severe asthma with an eosinophilic phenotype...
2016: Journal of Asthma and Allergy
Chieh-Hsin Wu, Zi-Hao Zhang, Ming-Kung Wu, Chiu-Huan Wang, Ying-Yi Lu, Chih-Lung Lin
BACKGROUND: Osteoporosis and migraine are both important public health problems and may have overlapping pathophysiological mechanisms. The aim of this study was to use a Taiwanese population-based dataset to assess migraine risk in osteoporosis patients. METHODS: The Taiwan National Health Insurance Research Database was used to analyse data for 40,672 patients aged ≥20 years who had been diagnosed with osteoporosis during 1996-2010. An additional 40,672 age-matched patients without osteoporosis were randomly selected as the non-osteoporosis group...
2016: SpringerPlus
Elena Priante, Laura Moschino, Veronica Mardegan, Paolo Manzoni, Sabrina Salvadori, Eugenio Baraldi
Despite notable advances in the survival and management of preterm infants in recent decades, chronic lung disease remains a common complication. Approximately one in three infants born preterm (< 32 weeks of gestation) are hospitalized with respiratory problems (mainly due to infections) in their first 2 years of life, and the risk of childhood wheezing is three times higher in this population. By comparison with infants born at term, there seems to be a higher incidence of respiratory morbidity in those born preterm, even in the absence of bronchopulmonary dysplasia (BPD) and in late-preterm babies...
September 2016: American Journal of Perinatology
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